1. Field of the Invention
The present invention refers to a new therapeutic use of uridine in the field of peripheral complications in diabetes mellitus.
2. Description of the Prior Art
Uridine is a known endogenous compound which has been studied in the past as a pharmacological agent in many experimental models, even those in no way related to each other. It has, in fact, been shown that cytidine and uridine are capable of prolonging the functional survival of an isolated cat brain. Other researchers have brought to light important anticonvulsive properties of uridine. More recently, uridine has been proposed as a substance promoting sleep, as a substitute for a renal natriuretic system, or as a dopaminergic modulator of the central nervous system.
It is furthermore universally known from classical biochemistry texts that uridine is the most important carrier of glucose within the cell, and that glycogen can only be formed upon intervention of uridine.
It has also been shown that cytidine and uridine are capable of converting the normal use of glucose in cirrhotic patients treated with insulin. It has furthermore been shown that uridine increases the formation of glycogen in the muscles and that uridine can antagonize certain effects due to insulin hypoglycemia.
The peripheral complications in diabetes mellitus include a number of disabling situations, such as neuropathy, retinopathy, vasculopathy, etc. due to the presence in the blood of high quantities of glucose, which can spread passively in all types of cell not provided with specific "carriers".
If the endocellular glucose exceeds the energy requirement, and is not stored in the form of polysaccharides, it can damage the cell, both because it changes into fructose and sorbitol (sugars which do not easily spread outwards, and which for this reason cause the cell to swell and lose functional activity), and because it can react with proteins and nucleic acids, bringing about a form of premature "cell aging".
To relieve the peripheral symptomatology of diabetes mellitus, certain drugs have recently been proposed in the field of therapy. These drugs, by inhibiting the enzyme "aldosoreductase", prevent the glucose from transforming itself into sorbitol, thus limiting the damage caused by cellular oedema (see for example Annual Reports in Medicinal Chemistry 19, 169-177, 1984). At least in short-term clinical tests, these compounds have shown themselves to be of use to antagonize diabetic neuropathies (see for example: Lancet II, 758-762, 1983; New England J. Medicine 316, 599-606, 1987). However, these synthetic derivatives are not without side-effects which could compromise their long-term use, as in theory the diabetic patient would have to be treated all his life. It is therefore necessary to find physiological compounds that, as well as being active, are also free from serious undesirable effects.